Control nucleic acid sequences may sometimes be used to facilitate assessment and/or analysis of nucleic acid sequencing data obtained in various ways, including using next-generation sequencing systems such as, for example, the Ion PGM™ and Ion Proton™ systems implementing Ion Torrent™ sequencing technology (see, e.g., U.S. Pat. No. 7,948,015 and U.S. Pat. Appl. Publ. Nos. 2010/0137143, 2009/0026082, and 2010/0282617, which are all incorporated by reference herein in their entirety). For example, certain relatively short (e.g., less than 100 base pairs) nucleic acid sequences constrained to contain homopolymers of only certain lengths (e.g., homopolymers of length two, three, or four; homopolymers of length no more than 2; or homopolymers of length no more than 1) may be used to attempt to assess potential error failure modes that may be related to homopolymer of such lengths and may more generally be indicative of performance. However, these nucleic acid sequences may in some cases be oversensitive and may not be able to properly capture or detect certain error modes of interest. There is a need for new and improved control nucleic acid sequences and methods for designing the same that can better facilitate assessment and/or analysis of nucleic acid sequencing data obtained using the above-mentioned systems or other sequencing systems/platforms.